The projects described in this application plan to examine various aspects of self-nonself discrimination with particular emphasis on mechanisms which may be involved in tumor immunity. Six different approaches to studying self-nonself recognition are proposed, based on the expertise of six groups of investigators. Through the use of cell adhesion techniques, Project I will probe the nature of malignancy by comparing adhesion characteristics of malignant cells with those of normal cells. Project II intends to examine participation of macrophages in in vitro models of tumor immunity by comparing induction of selective macrophage cytotoxicity against malignant but not normal cells. Project III employs immunochemical techniques to examine the structure of macrophage components and to relate understanding of the molecular nature of surface molecules to macrophage function in immune responses. A major aspect of self-nonself recognition manifests itself as the ability of the developing organism to recognize and become tolerant to self antigens, but not to nonself antigens, a process which will be studied in depth by Project IV. A failure of suppressor T cell regulatory influences, due to aberrations including malignant transformation, maybe responsible for development of autoimmunity, a problem Project V proposes to examine. Project VI plans to study the observed decrease in antibody-dependent, cell-mediated cytotoxicity in patients and animals with immune complex disease, as well as the nature and significance of immune complexes containing tumor antigens.